Post-Traumatic Epilepsy: Cellular Mechanisms and Implications for Treatment

Summary: Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme-containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate per-oxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving -y-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment.     

Quantification in Patient Urine Samples of Felbamate and Three Metabolites: Acid Carbamate and Two Mercapturic Acids

PURPOSE: Previously we proposed and provided evidence for the metabolic pathway of felbamate (FBM), which leads to the reactive metabolite, 3-carbamoyl-2-phenylpropion-aldehyde. This aldehyde carbamate was suggested to be the reactive intermediate in the oxidation of 2-phenyl-1,3-propanediol monocarbamate to the major human metabolite 3-carbamoyl-2-phenylpropionic acid. In addition, the aldehyde carbamate was found to undergo spontaneous elimination to 2-phenylpropenal, commonly known as atropaldehyde. Moreover, atropaldehyde was proposed to play a role in the development of toxicity during FBM therapy. Evidence for atropaldehyde formation in vivo was reported with the identification of modified N-acetyl-cysteine conjugates of atropaldehyde in both human and rat urine after FBM administration. Identification of the atropaldehyde-derived mercapturic acids in urine after FBM administration is consistent with the hypothesis that atropaldehyde is formed in vivo and that it reacts with thiol nucleophiles. Based on the hypothesis that the potential for toxicity will correlate to the amount of atropaldehyde formed, we sought to develop an analytic method that would quantify the amount of relevant metabolites excreted in patient urine. METHODS: We summarize the results of an LC/MS method used to quantify FBM, 3-carbamoyl-2-phenylpropionic acid and two atropaldehyde-derived mercapturic acids in the patient population. RESULTS: Analysis was performed on 31 patients undergoing FBM therapy. The absolute quantities of FBM and three metabolites were measured. CONCLUSIONS: This method demonstrated sufficient precision for the identification of patients exhibiting "abnormal" levels of atropaldehyde conjugates and may hold potential for patient monitoring.     

Non–Giant Cell Temporal Arteritis. Three Cases And a Review Of The Literature

We report two cases of polyarteritis and one of hypersensitivity angiitis diagnosed by temporal artery biopsy. Autopsies showed no evidence of giant cell arteritis. A review of the English literature provides seven further autopsy cases of necrotizing vasculitis diagnosed by temporal artery biopsy. The term temporal arteritis includes many types of vasculitis, giant cell arteritis being one of them.     

Differential effects of propranolol on lymphocyte rosette formation and response to plant mitogens

The effects of propranolol on various lymphocyte functions were studied to gain a better understanding of the recently demonstrated suppressive effect of propranolol on rheumatoid factor production. D- and L-propranolol at a concentration of 1 X 10⁻⁴ M inhibited the formation of human EA rosettes. The inhibition occurred within one minute of adding the compounds, was reversible, and did not affect cell viability. Addition of propranolol to preformed EA rosettes failed to disaggregate them. Patching and capping of SIg by an Fab′2 anti-IgG were inhibited at 2.5 X 10⁻⁵M and above. Propranolol at 2.5 X 10⁻⁵M also inhibited lymphocyte response to phytohemagglutinin and pokeweed mitogen without evidence of cell toxicity by trypan blue staining or absolute numbers of surviving cells. Congeners of propranolol with mainly beta adrenergic blocking properties did not show inhibitory effects. The inhibitory activities of propranolol are interpreted in terms of propranolol's membrane stabilizing effects and ability to interfere with membrane receptor movement.     

Radiation exposure from head computed tomography scans in pediatric trauma

Background

We have previously reported that children receive significantly less radiation exposure after abdominal and/or pelvis computed tomography (CT) scanning for acute appendicitis when performed at our children's hospital (CH) rather than at outside hospitals (OH). In this study, we compare the amount of radiation children receive from head CTs for trauma done at OH versus those at our CH.

Methods

A retrospective chart review was performed on all children transferred to our hospital after receiving a head CT for trauma at an OH between July 2012 and December 2012. These children were then blindly case matched based on date, age, and gender to children at our CH.

Results

There were 50 children who underwent head CT scans for trauma at 28 OH. There were 21 females and 29 males in each group. Average age was 7.01 ± 0.5 y at the OH and 7.14 ± 6.07 at our CH (P = 0.92). Average weight was 30.81 ± 4.69 kg at the OH and 32.69 ± 27.21 kg at our CH (P = 0.81). Radiation measures included dose length product (671.21 ± 22.6 mGycm at OH versus 786.28 ± 246.3 mGycm at CH, P = 0.11) and CT dose index (53.4 ± 2.26 mGy at OH versus 49.2 ± 12.94 mGy at CH, P = 0.56).

Conclusions

There is no significant difference between radiation exposure secondary to head CTs for traumatic injuries performed at OH and those at a dedicated CH.     

A programmed training technique that uses reinforcement to facilitate acquisition and retention in brain-damaged patients

Hospitalized brain-damaged patients were Ss in a study designed to evaluate the effectiveness of a treatment technique used with contingent reinforcement to facilitate acquisition and retention of environmentally relevant information. Ss were divided into three groups that were equated diagnostically and demographically. Group I received the treatment technique with contingent material and verbal reinforcement. Group II received the treatment technique with only contingent verbal reinforcement, and Group III was a control. Both treatment groups showed significant acquisition of the experimental information, and 1 week after training the two treatment groups showed no significant loss of acquired information. None of the groups showed any significant change in ward behavior during the experiment. It was concluded that the treatment technique used with contingent reinforcement can be used in the retraining of memory in brain-damaged patients.     

Changing negative attributions to mental patients by means of demythologizing seminars

As compared with a group of matched controls, psychiatric clients exposed to demythologizing seminars made significant and positive changes in the qualities that they attributed to the mental patient. Implications of this study for further research were discussed.     

A validational study of the WIST as a group-administered instrument for assessment of schizophrenic thinking

The objective assessment of thought disorder in schizophrenia is problem matic in clinical psychology. Recently and individually administered instrument (WIST) was introduced as a brief, objective, and quantitative measure of schizophrenic thought processes. Possible shortcomings of the WIST are noted; experimental findings that concern extension to group testing conditions, convergent validity with another self-report measure of schizophrenia, and discriminant validity from intellectual level are presented.     

Choice of defense mechanisms by indian and white adolescents

An analysis of Defense Mechanism Inventory scores from Indian and white adolescents indicated some cultural differences. Differences between white, male-female performance scores were found in all five defense categories. Differences between Indian, male-female performance scores were found for three of the five defense categories. Indian-white differences were found only for males and involved the two categoriee of turning against object and reversal. It was concluded that Indian child-rearing practices and culture may foster the development of reversal type defenses and inhibit the development of turning against object type defenses within Indian males.